Like many other eight-year-old girls, Virsaviya Borun-Goncharova loves to play, dance, sing, and draw. On the surface, she’s just a regular, high-energy school kid.
But something quite dramatic sets her apart from her peers: Virsaviya was born with her heart outside her chest.
Virsaviya has a condition called Pentalogy of Cantrell (POC), a rare disease characterized by a spectrum of congenital birth defects that can affect the sternum (breastbone), diaphragm, heart, and abdominal wall. In fact, Virsaviya has one of the most extreme forms of the condition: ectopia cordis, in which the heart forms outside the protective walls of the chest, leaving it exposed and vulnerable.
POC is extremely rare, affecting an estimated 1 to 2 in a million live births. The condition is often fatal without surgical intervention, which makes Virsaviya’s survival even more amazing.
“Doctors told me that my daughter would die before birth or during labor, but she defied the odds,” said Dari Borun, who is originally from Russia and now lives in Florida. “I like to call her my miracle and my warrior.”
Researchers still do not know what causes the unusual condition. But they’re working on it.
A research team headed by Bob Adelstein, M.D and Xuefei Ma, Ph.D., scientists in the Laboratory of Molecular Cardiology at NHLBI, are closely studying the underlying genetic mutations associated with the condition. Their ultimate goal is to find out what causes it, which may hold the key to finding a way to prevent or possibly treat the condition. Interestingly, Adelstein says he became interested in the condition a few years ago quite by chance.
“We were studying diseases related to non-muscle myosins, proteins that play a key role in development and cell division,” said Adelstein. “Using mice as a model system, we introduced a mutation in a myosin gene we already knew to be important in cardiac development.”
To their surprise, he said, the change resulted in a mouse dying prematurely with the heart outside of its body. Adelstein and his team found other cardiac and organ abnormalities as well.
But initially “we didn’t really know what we were looking at,” Adelstein said. “It just happened that a pediatric cardiologist was in the room at that time and recognized the condition as Pentalogy of Cantrell, a rare collection of abnormalities.”
The genetic mutation that Adelstein and Ma have since developed in mice fully duplicates the abnormalities of human POC. Now, together with The Collaborative Health Initiative Research Program (CHIRP) at the Naval Medical Center, they have undertaken the sequencing of the genomes of both POC patients and their families. Eventually, they want to find the human genes responsible for causing Virsaviya’s heart to form outside her chest.
The research team originally thought they might be able to identify a single mutation in humans with POC that would replicate the mouse model. But in studies sequencing genes from 28 families affected by POC, a single mutation that is common between even two of the families has yet to be identified. And this has led the researchers to believe that the condition might be caused by mutations in multiple genes, not just one. “We’ve just got to find the right ones,” Adelstein said, adding that he and his team are currently testing promising candidates in mice.
“Pentalogy of Cantrell is a lot more complicated than we realized in the beginning,” Adelstein said. To date their data suggests that the genetic defect in POC, including in Virsaviya’s case, is not inherited from the parents. In addition, environmental factors and drug interactions could be playing a role.
To get an even better handle on the condition, Adelstein’s team is continuing to collect tissue and saliva samples from as many POC patients and their immediate families as possible. The team already has obtained genetic samples from POC cases from all over the world. But “It’s not easy,” Adelstein said, “as these cases are so rare.”
“We could use help from other researchers around the world in identifying more cases.” The NIH Clinical Center is currently collecting blood or tissue samples from patients and their family members with POC. [https://clinicalcenter.nih.gov/recruit/protocols/04_pentalogy-of-cantrell.html]
When doctors do identify mutations that are causative for POC, they will be able to get a better understanding of the mechanisms underlying the collection of defects associated with POC. And this, in turn, will help open the door to a better understanding cardiac development in general, as well as other forms of congenital heart disease, Adelstein said.
Unfortunately, the current research might not benefit Virsaviya. At present the only treatment for POC is an early surgical intervention, followed by additional surgeries as a child grows older. However, defects in the heart structure often result in increased blood pressure in the lungs, making surgery too risky for some. The complexity and fragility of Virsaviya’s own condition have led doctors to rule out surgery for now.
But she forges on. During the day or when at play, Virsaviya protects her heart with a custom-made chest protector to guard against accidental bumps. And she gets regular doctor checkups to prevent things from going wrong. Despite her delicate circumstances, she appears strong, happy, and energetic—just like any other kid her age.
“I love my daughter the way she is. That’s the way God made her,” said her mother Dari. “But I don’t want this condition to happen to other kids if it can be prevented. I support the work of NHLBI researchers to continue to shed light on this condition and perhaps find a way to treat it.”